rsi ad
 
drx ad
 
ad space

Mometasone Furoate Monohydrate Nasal Spray

FOR INTRANASAL USE ONLY

TABLE OF CONTENTS

1. DESCRIPTION 7. WARNINGS AND PRECAUTIONS
2. INDICATIONS AND USAGE 8. ADVERSE REACTIONS
3. DOSAGE AND ADMINISTRATION 9. OVERDOSAGE
4. CONTRAINDICATIONS 10. DRUG INTERACTIONS
5. MECHANISM OF ACTION 11. PHARMACOKINETICS
6. USE IN SPECIFIC POPULATIONS 12. HOW SUPPLIED/STORAGE AND HANDLING


1. DESCRIPTION

Mometasone furoate monohydrate, the active component of Mometasone Furoate Monohydrate Nasal Spray, 50 mcg, is an anti-inflammatory corticosteroid.

Mometasone furoate monohydrate has a chemical name of 9,21-Dichloro-11ß,17-dihydroxy-16a-methylpregna-1,4-diene-3,20-dione 17-(2 furoate) monohydratean. Its empirical formula of C27H30Cl2O6•H2O, molecular weight of 539.45, and has the following chemical structure:

Mometasone furoate monohydrate is a white powder. It is practically insoluble in water; slightly soluble in methanol, ethanol, and isopropanol; soluble in acetone and chloroform; and freely soluble in tetrahydrofuran. Its partition coefficient between octanol and water is greater than 5000.

Mometasone Furoate Monohydrate Nasal Spray, 50 mcg is a metered-dose, manual pump spray unit containing an aqueous suspension of mometasone furoate monohydrate equivalent to 0.05% w/w mometasone furoate calculated on the anhydrous basis; in an aqueous medium containing glycerin, microcrystalline cellulose and carboxymethylcellulose sodium, sodium citrate, citric acid, benzalkonium chloride, and polysorbate 80. The pH is between 4.3 and 4.9.

After initial priming (10 actuations), each actuation of the pump delivers a metered spray containing 100 mg of suspension containing mometasone furoate monohydrate equivalent to 50 mcg of mometasone furoate calculated on the anhydrous basis. Each bottle of Mometasone Furoate Monohydrate Nasal Spray, 50 mcg provides 120 sprays.

2. INDICATIONS AND USAGE

2.1 Treatment of Allergic Rhinitis

Mometasone Furoate Monohydrate Nasal Spray 50 mcg is indicated for the treatment of the nasal symptoms of seasonal allergic and perennial allergic rhinitis, in adults and pediatric patients 2 years of age and older.

2.2 Treatment of Nasal Congestion Associated with Seasonal Allergic Rhinitis

Mometasone Furoate Monohydrate Nasal Spray 50 mcg is indicated for the relief of nasal congestion associated with seasonal allergic rhinitis, in adults and pediatric patients 2 years of age and older.

2.3 Prophylaxis of Seasonal Allergic Rhinitis

Mometasone Furoate Monohydrate Nasal Spray 50 mcg is indicated for the prophylaxis of the nasal symptoms of seasonal allergic rhinitis in adult and adolescent patients 12 years and older.

2.4 Treatment of Nasal Polyps

Mometasone Furoate Monohydrate Nasal Spray 50 mcg is indicated for the treatment of nasal polyps in patients 18 years of age and older.

3. DOSAGE AND ADMINISTRATION

Administer Mometasone Furoate Monohydrate Nasal Spray 50 mcg by the intranasal route only. Prior to initial use of Mometasone Furoate Monohydrate Nasal Spray, 50 mcg, the pump must be primed by actuating ten times or until a fine spray appears. The pump may be stored unused for up to 1 week without repriming. If unused for more than 1 week, reprime by actuating two times, or until a fine spray appears.

3.1 Treatment of Allergic Rhinitis

Adults and Adolescents 12 Years of Age and Older:

The recommended dose for treatment of the nasal symptoms of seasonal allergic and perennial allergic rhinitis is 2 sprays (50 mcg of mometasone furoate in each spray) in each nostril once daily (total daily dose of 200 mcg).

Children 2 to 11 Years of Age:

The recommended dose for treatment of the nasal symptoms of seasonal allergic and perennial allergic rhinitis is 1 spray (50 mcg of mometasone furoate in each spray) in each nostril once daily (total daily dose of 100 mcg).

3.2 Treatment of Nasal Congestion Associated with Seasonal Allergic Rhinitis

Adults and Adolescents 12 Years of Age and Older:

The recommended dose for treatment of nasal congestion associated with seasonal allergic rhinitis is two sprays (50 mcg of mometasone furoate in each spray) in each nostril once daily (total daily dose of 200 mcg).

Children 2 to 11 Years of Age:

The recommended dose for treatment of nasal congestion associated with seasonal allergic rhinitis is one spray (50 mcg of mometasone furoate in each spray) in each nostril once daily (total daily dose of 100 mcg).

3.3 Prophylaxis of Seasonal Allergic Rhinitis

Adults and Adolescents 12 Years of Age and Older:

The recommended dose for prophylaxis treatment of nasal symptoms of seasonal allergic rhinitis is 2 sprays (50 mcg of mometasone furoate in each spray) in each nostril once daily (total daily dose of 200 mcg).

In patients with a known seasonal allergen that precipitates nasal symptoms of seasonal allergic rhinitis, prophylaxis with Mometasone Furoate Monohydrate Nasal Spray 50 mcg (200 mcg/day) is recommended 2 to 4 weeks prior to the anticipated start of the pollen season.

3.4 Treatment of Nasal Polyps

Adults 18 Years of Age and Older:

The recommended dose for the treatment of nasal polyps is 2 sprays (50 mcg of mometasone furoate in each spray) in each nostril twice daily (total daily dose of 400 mcg). A dose of 2 sprays (50 mcg of mometasone furoate in each spray) in each nostril once daily (total daily dose of 200 mcg) is also effective in some patients.

4. CONTRAINDICATIONS

Hypersensitivity to any of the ingredients of this preparation contraindicates its use.

5. MECHANISM OF ACTION

The precise mechanism of corticosteroid action on allergic rhinitis is not known. Corticosteroids have been shown to have a wide range of effects on multiple cell types (eg, mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (eg, histamine, eicosanoids, leukotrienes, and cytokines) involved in inflammation.

6. USE IN SPECIFIC POPULATIONS

6.1 Usage in Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. This drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

6.2 Nursing Mothers

It is not known if mometasone furoate is excreted in human milk. Because other corticosteroids are excreted in human milk, caution should be used when Mometasone Furoate Monohydrate Nasal Spray, 50 mcg is administered to nursing women.

6.3 Pediatric Use

Safety and effectiveness of Mometasone Furoate Monohydrate Nasal Spray, 50 mcg in pediatric patients less than 2 years of age have not been established.

6.4 Geriatric Use

The adverse reactions reported in this population were similar in type and incidence to those reported by younger patients.

7. WARNINGS AND PRECAUTIONS

7.1 Local Nasal Effects

Epistaxis

In clinical studies, epistaxis was observed more frequently in patients with allergic rhinitis with Mometasone Furoate Monohydrate Nasal Spray than those who received placebo [see Adverse Reactions].

Candida Infection

In clinical studies with Mometasone Furoate Monohydrate Nasal Spray 50 mcg, the development of localized infections of the nose and pharynx with Candida albicans has occurred. When such an infection develops, use of Mometasone Furoate Monohydrate Nasal Spray 50 mcg should be discontinued and appropriate local or systemic therapy instituted, if needed.

Nasal Septum Perforation

Instances of nasal septum perforation have been reported following the intranasal application of corticosteroids. As with any long-term topical treatment of the nasal cavity, patients using Mometasone Furoate Monohydrate Nasal Spray 50 mcg over several months or longer should be examined periodically for possible changes in the nasal mucosa.

Impaired Wound Healing

Because of the inhibitory effect of corticosteroids on wound healing, patients who have experienced recent nasal septum ulcers, nasal surgery, or nasal trauma should not use a nasal corticosteroid until healing has occurred.

7.2 Glaucoma and Cataracts

Nasal and inhaled corticosteroids may result in the development of glaucoma and/or cataracts. Therefore, close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts.

Glaucoma and cataract formation was evaluated in one controlled study of 12 weeks’ duration and one uncontrolled study of 12 months’ duration in patients treated with Mometasone Furoate Monohydrate Nasal Spray, 50 mcg at 200 mcg/day, using intraocular pressure measurements and slit lamp examination. No significant change from baseline was noted in the mean intraocular pressure measurements for the 141 Mometasone Furoate Monohydrate-treated patients in the 12-week study, as compared with 141 placebo-treated patients. No individual Mometasone Furoate Monohydrate-treated patient was noted to have developed a significant elevation in intraocular pressure or cataracts in this 12-week study. Likewise, no significant change from baseline was noted in the mean intraocular pressure measurements for the 139 Mometasone Furoate Monohydrate-treated patients in the 12-month study and again, no cataracts were detected in these patients. Nonetheless, nasal and inhaled corticosteroids have been associated with the development of glaucoma and/or cataracts.

7.3 Hypersensitivity Reactions

Hypersensitivity reactions including instances of wheezing may occur after the intranasal administration of mometasone furoate monohydrate. Discontinue Nasonex Nasal Spray if such reactions occur [see Contraindications].

7.4 Immunosuppression

Persons who are on drugs which suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in nonimmune children or adults on corticosteroids. In such children or adults who have not had these diseases, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If exposed to chickenpox, prophylaxis with varicella zoster immune globin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chickenpox develops, treatment with antiviral agents may be considered.

Corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculous infection of the respiratory tract, or in untreated fungal, bacterial, systemic viral infections, or ocular herpes simplex because of the potential for worsening of these infections.

7.5 Hypothalamic-Pituitary-Adrenal Axis Effect

Hypercorticism and Adrenal Suppression

When intranasal steroids are used at higher than recommended dosages or in susceptible individuals at recommended dosages, systemic corticosteroid effects such as hypercorticism and adrenal suppression may appear. If such changes occur, the dosage of Nasonex Nasal Spray should be discontinued slowly, consistent with accepted procedures for discontinuing oral corticosteroid therapy.

7.6 Effect on Growth

Corticosteroids may cause a reduction in growth velocity when administered to pediatric patients. Monitor the growth routinely of pediatric patients receiving Mometasone Furoate Monohydrate Nasal Spray. To minimize the systemic effects of intranasal corticosteroids, including Mometasone Furoate Monohydrate Nasal Spray, titrate each patient’s dose to the lowest dosage that effectively controls his/her symptoms [see Use in Specific Populations].

8. ADVERSE REACTIONS

Systemic and local corticosteroid use may result in the following:

• Epistaxis, ulcerations, Candida albicans infection, impaired wound healing [see Warnings and Precautions].

• Cataracts and glaucoma [see Warnings and Precautions]

• Immunosuppression [see Warnings and Precautions]

• Hypothalamic-pituitary-adrenal (HPA) axis effects, including growth reduction [see Warnings and Precautions, Use in Specific Populations]

8.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Allergic Rhinitis

Adults and adolescents 12 years of age and older

In controlled US and international clinical studies, a total of 3210 adult and adolescent patients 12 years and older with allergic rhinitis received treatment with Mometasone Furoate Monohydrate Nasal Spray 50 mcg at doses of 50 to 800 mcg/day. The majority of patients (n = 2103) were treated with 200 mcg/day. A total of 350 adult and adolescent patients have been treated for one year or longer. Adverse events did not differ significantly based on age, sex, or race. Four percent or less of patients in clinical trials discontinued treatment because of adverse events and the discontinuation rate was similar for the vehicle and active comparators.

All adverse events (regardless of relationship to treatment) reported by 5% or more of adult and adolescent patients ages 12 years and older who received Mometasone Furoate Monohydrate Nasal Spray 50 mcg, 200 mcg/day vs. placebo and that were more common with Mometasone Furoate Monohydrate Nasal Spray 50 mcg than placebo, are displayed in TABLE 1 below.

TABLE 1. ADULT AND ADOLESCENT PATIENTS 12 YEARS AND OLDER – ADVERSE EVENTS FROM CONTROLLED CLINICAL TRIALS IN SEASONAL ALLERGIC AND PERENNIAL ALLERGIC RHINITIS (PERCENT OF PATIENTS REPORTING)

Other adverse events which occurred in less than 5% but greater than or equal to 2% of adult and adolescent patients (ages 12 years and older) treated with Mometasone Furoate Monohydrate Nasal Spray 50 mcg, 200-mcg/day (regardless of relationship to treatment), and more frequently than in the placebo group included: arthralgia, asthma, bronchitis, chest pain, conjunctivitis, diarrhea, dyspepsia, earache, flu-like symptoms, myalgia, nausea, and rhinitis.

Pediatric patients < 12 years of age

In controlled US and international studies, a total of 990 pediatric patients (ages 3 to 11 years) with allergic rhinitis received treatment with Mometasone Furoate Monohydrate Nasal Spray 50 mcg, at doses of 25 to 200 mcg/day. The majority of pediatric patients (n = 720) were treated with 100 mcg/day. A total of 163 pediatric patients have been treated for one year or longer. Two percent or less of patients in clinical trials who received Mometasone Furoate Monohydrate Nasal Spray 50 mcg discontinued treatment because of adverse events and the discontinuation rate was similar for the placebo and active comparators.

Adverse events which occurred in ≥5% of pediatric patients (ages 3 to 11 years) treated with Mometasone Furoate Monohydrate Nasal Spray 50 mcg, 100 mcg/day vs. placebo (regardless of relationship to treatment) and more frequently than in the placebo group included upper respiratory tract infection (5% in Mometasone Furoate Monohydrate Nasal Spray 50 mcg group vs. 4% in placebo) and vomiting (5% in Mometasone Furoate Monohydrate Nasal Spray 50 mcg group vs. 4% in placebo).

Other adverse events which occurred in less than 5% but greater than or equal to 2% of pediatric patients (ages 3 to 11 years) treated Mometasone Furoate Monohydrate Nasal Spray 50 mcg, 100-mcg/day vs. placebo (regardless of relationship to treatment) and more frequently than in the placebo group included: diarrhea, nasal irritation, otitis media, and wheezing.

The adverse event (regardless of relationship to treatment) reported by 5% of pediatric patients ages 2 to 5 years who received Mometasone Furoate Monohydrate Nasal Spray, 50 mcg, 100 mcg/day in a clinical trial vs. placebo including 56 subjects (28 each Mometasone Furoate Monohydrate Nasal Spray, 50 mcg and placebo) and that was more common with Mometasone Furoate Monohydrate Nasal Spray, 50 mcg than placebo, included: upper respiratory tract infection (7% vs. 0%, respectively). The other adverse event which occurred in less than 5% but greater than or equal to 2% of mometasone furoate pediatric patients ages 2 to 5 years treated with 100-mcg doses vs. placebo (regardless of relationship to treatment) and more frequently than in the placebo group included: skin trauma.

8.2 Post-Marketing Experience

The following adverse reactions have been identified during the post-marketing period for Mometasone Furoate Monohydrate Nasal Spray 50 mcg: nasal burning and irritation, anaphylaxis and angioedema, disturbances in taste and smell and nasal septal perforation. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

9. OVERDOSAGE

There are no data available on the effects of acute or chronic overdosage with NASONEX Nasal Spray 50 mcg. Because of low systemic bioavailability, and an absence of acute drug-related systemic findings in clinical studies, overdose is unlikely to require any therapy other than observation. Intranasal administration of 1600 mcg (4 times the recommended dose of NASONEX Nasal Spray 50 mcg for the treatment of nasal polyps in patients 18 years of age and older) daily for 29 days, to healthy human volunteers, showed no increased incidence of adverse events. Single intranasal doses up to 4000 mcg and oral inhalation doses up to 8000 mcg have been studied in human volunteers with no adverse effects reported. Chronic over dosage with any corticosteroid may result in signs or symptoms of hypercorticism [see Warnings and Precautions]. Acute overdosage with this dosage form is unlikely since one bottle of NASONEX Nasal Spray 50 mcg contains approximately 8500 mcg of mometasone furoate.

10. DRUG INTERACTIONS

No formal drug-drug interaction studies have been conducted with NASONEX Nasal Spray 50 mcg.

Inhibitors of Cytochrome P450 3A4: Studies have shown that mometasone furoate is primarily and extensively metabolized in the liver of all species investigated and undergoes extensive metabolism to multiple metabolites. In vitro studies have confirmed the primary role of cytochrome CYP 3A4 in the metabolism of this compound. Coadministration with ketoconazole, a potent CYP 3A4 inhibitor, may increase the plasma concentrations of mometasone furoate.

11. PHARMACOKINETICS

Absorption: Mometasone furoate monohydrate administered as a nasal spray is virtually undetectable in plasma from adult and pediatric subjects despite the use of a sensitive assay with a lower quantitation limit (LOQ) of 50 pcg/mL.

Distribution: The in vitro protein binding for mometasone furoate was reported to be 98% to 99% in concentration range of 5 to 500 ng/mL.

Metabolism: Studies have shown that any portion of a mometasone furoate dose which is swallowed and absorbed undergoes extensive metabolism to multiple metabolites. There are no major metabolites detectable in plasma. Upon in vitro incubation, one of the minor metabolites formed is 6ß-hydroxymometasone furoate. In human liver microsomes, the formation of the metabolite is regulated by cytochrome P-450 3A4 (CYP3A4).

Elimination: Following intravenous administration, the effective plasma elimination half-life of mometasone furoate is 5.8 hours. Any absorbed drug is excreted as metabolites mostly via the bile, and to a limited extent, into the urine.

Special Populations: The effects of renal impairment, hepatic impairment, age, or gender on mometasone furoate pharmacokinetics have not been adequately investigated.

12. HOW SUPPLIED/STORAGE AND HANDLING

1) How Available:

a) Brand name: NASONEX, by SCHERING PLOUGH.

b) Generic drugs: None.

2) How Supplied:

NASONEX (mometasone furoate monohydrate) Nasal Spray, 50 mcg is supplied in a white, high-density, polyethylene bottle fitted with a white metered-dose, manual spray pump, and blue cap. It contains 17 g of product formulation, 120 sprays, each delivering 50 mcg of mometasone furoate per actuation. Supplied with Patient’s Instructions for Use (NDC 0085-1288-01).

3) Storage: Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F). Protect from light.

When NASONEX Nasal Spray, 50 mcg is removed from its cardboard container, prolonged exposure of the product to direct light should be avoided. Brief exposure to light, as with normal use, is acceptable.

SHAKE WELL BEFORE EACH USE.

Rx only

Rev 01/11